國家衛生研究院 NHRI:Item 3990099045/15240
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    题名: A multi-ancestry polygenic risk score for coronary heart disease based on an ancestrally diverse genome-wide association study and population-specific optimization
    作者: Smith, JL;Tcheandjieu, C;Dikilitas, O;Iyer, K;Miyazawa, K;Hilliard, A;Lynch, J;Rotter, JI;Chen, Y-DI;Sheu, WH-H;Chang, K-M;Kanoni, S;Tsao, P;Ito, K;Kosel, M;Clarke, SL;Schaid, DJ;Assimes, TL;Kullo, IJ
    贡献者: Institute of Molecular and Genomic Medicine
    摘要: Background Predictive performance of polygenic risk scores (PRS) varies across populations. To facilitate equitable clinical use, we developed PRS for coronary heart disease (PRSCHD) for 5 genetic ancestry groups.Methods We derived ancestry-specific and multi-ancestry PRSCHD based on pruning and thresholding (PRSP+T) and continuous shrinkage priors (PRSCSx) applied on summary statistics from the largest multi-ancestry genome-wide meta-analysis for CHD to date, including 1.1 million participants from 5 continental populations. Following training and optimization of PRSCHD in the Million Veteran Program, we evaluated predictive performance of the best performing PRSCHD in 176,988 individuals across 9 cohorts of diverse genetic ancestry.Results Multi-ancestry PRSP+T outperformed ancestry specific PRSP+T across a range of tuning values. In training stage, for all ancestry groups, PRSCSx performed beter than PRSP+T and multi-ancestry PRS outperformed ancestry-specific PRS. In independent validation cohorts, the selected multi-ancestry PRSP+T demonstrated the strongest association with CHD in individuals of South Asian (SAS) and European (EUR) ancestry (OR per 1SD[95% CI]; 2.75[2.41-3.14], 1.65[1.59-1.72]), followed by East Asian (EAS) (1.56[1.50-1.61]), Hispanic/Latino (HIS) (1.38[1.24-1.54]), and weakest in African (AFR) ancestry (1.16[1.11-1.21]). The selected multi-ancestry PRSCSx showed stronger association with CHD in comparison within each ancestry group where the association was strongest in SAS (2.67[2.38-3.00]) and EUR (1.65[1.59-1.71]), progressively decreasing in EAS (1.59[1.54-1.64]), HIS (1.51[1.35-1.69]), and lowest in AFR (1.20[1.15-1.26]).Conclusions Utilizing diverse summary statistics from a large multi-ancestry genome-wide meta-analysis led to improved performance of PRSCHD in most ancestry groups compared to single-ancestry methods. Improvement of predictive performance was limited, specifically in AFR and HIS, despite use of one of the largest and most diverse set of training and validation cohorts to date. This highlights the need for larger GWAS datasets of AFR and HIS individuals to enhance performance of PRSCHD.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis work was supported by grants from the Polygenic Risk Methods in Diverse Populations (PRIMED) Consortium through the National Human Genome Research Institute (NHGRI): grant U01 HG11710, the electronic Medical Records and Genomics (eMERGE) Network funded by the NHGRI: grant U01 HG06379, a National Heart, Lung, and Blood: grant K24 HL137010, the Clinical Genome Resource (ClinGEN) funded by the NHGRI: grant HG09650, and R35 GM140487.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The Ethics committees/IRBS of the Million Veteran Program, the Ethics committees/IRBS of 10 academic sites including Mayo Clinic of The eMERGE Network, the ethics committees/IRBs of the UK Biobank, ethics committees/IRBs of the TAICHI Consortium, and the ethics committees/IRBs/NIH Data Access Committee of dbGaP gave Mayo Clinic and Stanford University ethical approval for this work.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement n the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesAll data produced in the present work are contained in the manuscript
    日期: 2023-06-06
    關聯: medRxiv. 2023 Jun 06;Article in Press.
    Link to: http://dx.doi.org/10.1101/2023.06.02.23290896
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